Back to Search
Start Over
Development of pH-Independent Drug Release Formulation Using Lipocalin-Type Prostaglandin D Synthase.
- Source :
-
Journal of pharmaceutical sciences [J Pharm Sci] 2016 Sep; Vol. 105 (9), pp. 2735-2742. Date of Electronic Publication: 2016 Jan 25. - Publication Year :
- 2016
-
Abstract
- The purpose of this study was to develop a pH-independent drug release formulation using lipocalin-type prostaglandin D synthase, a member of the lipocalin superfamily, with the function of forming complexes together with various small lipophilic molecules. Dipyridamole, a poorly water-soluble drug, showing a pH-dependent solubility profile, was used as the model drug. The solubilization of dipyridamole was achieved by a simple complex formulation method with lipocalin-type prostaglandin D synthase. The complex formulation was produced successfully by spray drying, and the obtained powder formulation showed complete dissolution in fasted-state simulated gastric fluid (pH, 1.6) and phosphate-buffered solution (pH, 6.8). In addition, the potential stability of the complex formulation was assessed, and the dissolution profile of the produced powder at pH 6.8 was maintained after 4-week storage under several storage conditions. Furthermore, a pharmacokinetic study using hypochlorhydria model rats was performed to verify the improvement of the intestinal absorption behavior, and eventually the complex formulation overcame the problematic absorption profile of dipyridamole in the elevated gastric pH conditions. These results, taken together, demonstrate that the use of this well-designed drug-delivery carrier is feasible for the development of pH-independent drug release formulations.<br /> (Copyright © 2016. Published by Elsevier Inc.)
- Subjects :
- Animals
Dipyridamole administration & dosage
Dipyridamole chemistry
Dipyridamole pharmacology
Drug Compounding
Drug Liberation
Drug Stability
Excipients
Humans
Hydrogen-Ion Concentration
Intestinal Absorption
Male
Models, Molecular
Platelet Aggregation Inhibitors administration & dosage
Platelet Aggregation Inhibitors chemistry
Platelet Aggregation Inhibitors pharmacology
Rats
Rats, Sprague-Dawley
Recombinant Proteins
Solubility
Intramolecular Oxidoreductases chemistry
Lipocalins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6017
- Volume :
- 105
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 26886322
- Full Text :
- https://doi.org/10.1016/S0022-3549(15)00176-8